Temperament clusters in a normal population: implications for health and disease

Background

The object of this study was to identify temperament patterns in the Finnish population, and to determine the relationship between these profiles and life habits, socioeconomic status, and health.

Methods/Principal Findings

A cluster analysis of the Temperament and Character Inventory subscales was performed on 3,761 individuals from the Northern Finland Birth Cohort 1966 and replicated on 2,097 individuals from the Cardiovascular Risk in Young Finns study. Clusters were formed using the k-means method and their relationship with 115 variables from the areas of life habits, socioeconomic status and health was examined.

Results

Four clusters were identified for both genders. Individuals from Cluster I are characterized by high persistence, low extravagance and disorderliness. They have healthy life habits, and lowest scores in most of the measures for psychiatric disorders. Cluster II individuals are characterized by low harm avoidance and high novelty seeking. They report the best physical capacity and highest level of income, but also high rate of divorce, smoking, and alcohol consumption. Individuals from Cluster III are not characterized by any extreme characteristic. Individuals from Cluster IV are characterized by high levels of harm avoidance, low levels of exploratory excitability and attachment, and score the lowest in most measures of health and well-being.

Conclusions

This study shows that the temperament subscales do not distribute randomly but have an endogenous structure, and that these patterns have strong associations to health, life events, and well-being.     

Biotin IgM Antibodies in Human Blood: A Previously Unknown Factor Eliciting False Results in Biotinylation-Based Immunoassays

Biotin is an essential vitamin that binds streptavidin or avidin with high affinity and specificity. As biotin is a small molecule that can be linked to proteins without affecting their biological activity, biotinylation is applied widely in biochemical assays. In our laboratory, IgM enzyme immuno assays (EIAs) of μ-capture format have been set up against many viruses, using as antigen biotinylated virus like particles (VLPs) detected by horseradish peroxidase-conjugated streptavidin. We recently encountered one serum sample reacting with the biotinylated VLP but not with the unbiotinylated one, suggesting in human sera the occurrence of biotin-reactive antibodies. In the present study, we search the general population (612 serum samples from adults and 678 from children) for IgM antibodies reactive with biotin and develop an indirect EIA for quantification of their levels and assessment of their seroprevalence. These IgM antibodies were present in 3% adults regardless of age, but were rarely found in children. The adverse effects of the biotin IgM on biotinylation-based immunoassays were assessed, including four inhouse and one commercial virus IgM EIAs, showing that biotin IgM do cause false positivities. The biotin can not bind IgM and streptavidin or avidin simultaneously, suggesting that these biotin-interactive compounds compete for the common binding site. In competitive inhibition assays, the affinities of biotin IgM antibodies ranged from 2.1×10(-3) to 1.7×10(-4 )mol/L. This is the first report on biotin antibodies found in humans, providing new information on biotinylation-based immunoassays as well as new insights into the biomedical effects of vitamins.     

c-Jun N-Terminal Kinase Phosphorylation of MARCKSL1 Determines Actin Stability and Migration in Neurons and in Cancer Cells

Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated migration underlies neurological birth defects and cancer metastasis. MARCKS-like protein 1 (MARCKSL1) is widely expressed in nervous tissue, where, like Jun N-terminal protein kinase (JNK), it is required for neural tube formation, though the mechanism is unknown. Here we show that MARCKSL1 is directly phosphorylated by JNK on C-terminal residues (S120, T148, and T183). This phosphorylation enables MARCKSL1 to bundle and stabilize F-actin, increase filopodium numbers and dynamics, and retard migration in neurons. Conversely, when MARCKSL1 phosphorylation is inhibited, actin mobility increases and filopodium formation is compromised whereas lamellipodium formation is enhanced, as is cell migration. We find that MARCKSL1 mRNA is upregulated in a broad range of cancer types and that MARCKSL1 protein is strongly induced in primary prostate carcinomas. Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state; phosphomimetic MARCKSL1 (MARCKSL1(S120D,T148D,T183D)) inhibits whereas dephospho-MARCKSL1(S120A,T148A,T183A) induces migration. In summary, these data show that JNK phosphorylation of MARCKSL1 regulates actin homeostasis, filopodium and lamellipodium formation, and neuronal migration under physiological conditions and that, when ectopically expressed in prostate cancer cells, MARCKSL1 again determines cell movement.     

High lactose tolerance in North Europeans: a result of migration, not in situ milk consumption

The main carbohydrate in milk is lactose, which must be hydrolyzed to glucose and galactose before the sugars can be digested. While 65% or more of the total human population are lactose intolerant, in some human populations lactase activity commonly persists into adulthood. Lactose tolerance is exceptionally widespread in Northern European countries such as Sweden and Finland, with tolerance levels of 74% and 82%, respectively. Theoretically, this may result either from a strong local selection pressure for lactose tolerance, or from immigration of lactose tolerant people to Northern Europe. We provide several lines of archaeological and historical evidence suggesting that the high lactose tolerance in North Europeans cannot be explained by selection from in situ milk consumption. First, fresh cow milk has not belonged to the traditional diet of Swedes or Finns until recent times. Second, not enough milk has been available for adult consumption. Cattle herding has been neither widespread nor productive enough in Northern Europe to have provided constant access to fresh milk. We suggest that the high prevalence of lactose tolerance in Finland in particular may be explained by immigration of people representing so-called Corded Ware Culture, an early culture representing agricultural development in Europe.     

Redox-dependent sodium binding by the Na(+)-translocating NADH:quinone oxidoreductase from Vibrio harveyi

Relaxation characteristics of the 23Na nuclei magnetization were used to determine the sodium-binding properties of the Na+-translocating NADH:quinone oxidoreductase from Vibrio harveyi (NQR). The dissociation constant of Na+ for the oxidized enzyme was found to be 24 mM and for the reduced enzyme about 30 microM. Such large (3 orders in magnitude) redox dependence of the NQR affinity to sodium ions shows that the molecular machinery was designed to use the drop in redox energy for creating an electrochemical sodium gradient. Redox titration of NQR monitored by changes in line width of the 23Na NMR signal at 2 mM Na+ showed that the enzyme affinity to sodium ions follows the Nernst law for a one-electron carrier with Em about -300 mV (vs SHE). The data indicate that energy conservation by NQR involves a mechanism modulating ion affinity by the redox state of an enzyme redox cofactor.     

Chromosome X-Wide Association Study Identifies Loci for Fasting Insulin and Height and Evidence for Incomplete Dosage Compensation

The X chromosome (chrX) represents one potential source for the “missing heritability” for complex phenotypes, which thus far has remained underanalyzed in genome-wide association studies (GWAS). Here we demonstrate the benefits of including chrX in GWAS by assessing the contribution of 404,862 chrX SNPs to levels of twelve commonly studied cardiometabolic and anthropometric traits in 19,697 Finnish and Swedish individuals with replication data on 5,032 additional Finns. By using a linear mixed model, we estimate that on average 2.6% of the additive genetic variance in these twelve traits is attributable to chrX, this being in proportion to the number of SNPs in the chromosome. In a chrX-wide association analysis, we identify three novel loci: two for height (rs182838724 near FGF16/ATRX/MAGT1, joint P-value = 2.71×10⁻⁹, and rs1751138 near ITM2A, P-value = 3.03×10⁻¹⁰) and one for fasting insulin (rs139163435 in Xq23, P-value = 5.18×10⁻⁹). Further, we find that effect sizes for variants near ITM2A, a gene implicated in cartilage development, show evidence for a lack of dosage compensation. This observation is further supported by a sex-difference in ITM2A expression in whole blood (P-value = 0.00251), and is also in agreement with a previous report showing ITM2A escapes from X chromosome inactivation (XCI) in the majority of women. Hence, our results show one of the first links between phenotypic variation in a population sample and an XCI-escaping locus and pinpoint ITM2A as a potential contributor to the sexual dimorphism in height. In conclusion, our study provides a clear motivation for including chrX in large-scale genetic studies of complex diseases and traits.     

Exploring Causality between TV Viewing and Weight Change in Young and Middle-Aged Adults. The Cardiovascular Risk in Young Finns Study

Background

Television viewing time (TV time) is associated with increased weight and obesity, but it is unclear whether this relation is causal.

Methods and Results

We evaluated changes in TV time, waist circumference (waist) and body mass index (BMI) in participants of the population-based Cardiovascular Risk in Young Finns study (761 women, 626 men aged 33–50 years in 2011). Waist and BMI were measured, and TV time was self-reported in 2001, 2007, and 2011. Changes in waist and BMI between 2001 and 2011 were studied a) for the whole group, b) in groups with constantly low (≤1 h/d), moderate (1–3 h/d), or high (≥3 h/d) TV time, and c) in groups with ≥1 hour in-/decrease in daily TV time between 2001 and 2011. BMIs in 1986 were also evaluated. We explored the causal relationship of TV time with waist and BMI by classical temporality criterion and recently introduced causal-discovery algorithms (pairwise causality measures). Both methods supported the hypothesis that TV time is causative to weight gain, and no evidence was found for reverse or bidirectional causality. Constantly low TV time was associated with less pronounced increase in waist and BMI, and waist and BMI increase was lower with decreased TV time (P<0.05). The increase in waist and BMI was at least 2-fold in the high TV time group compared to the low TV time group (P<0.05). Adjustment for age, sex, BMI/waist in 2001, physical activity, energy intake, or smoking did not change the results.

Conclusions

In young and middle-aged adults, constantly high TV time is temporally antecedent to BMI and waist increase.     

Experimental Infection of Voles with Francisella tularensis Indicates Their Amplification Role in Tularemia Outbreaks

Tularemia outbreaks in humans have been linked to fluctuations in rodent population density, but the mode of bacterial maintenance in nature is unclear. Here we report on an experiment to investigate the pathogenesis of Francisella tularensis infection in wild rodents, and thereby assess their potential to spread the bacterium. We infected 20 field voles (Microtus agrestis) and 12 bank voles (Myodes glareolus) with a strain of F. tularensis ssp. holarctica isolated from a human patient. Upon euthanasia or death, voles were necropsied and specimens collected for histological assessment and identification of bacteria by immunohistology and PCR. Bacterial excretion and a rapid lethal clinical course with pathological changes consistent with bacteremia and tissue necrosis were observed in infected animals. The results support a role for voles as an amplification host of F. tularensis, as excreta and, in particular, carcasses with high bacterial burden could serve as a source for environmental contamination.     

Moose (Alces alces) reacts to high summer temperatures by utilizing thermal shelters in boreal forests – an analysis based on airborne laser scanning of the canopy structure at moose locations

The adaptation of different species to warming temperatures has been increasingly studied. Moose (Alces alces) is the largest of the ungulate species occupying the northern latitudes across the globe, and in Finland it is the most important game species. It is very well adapted to severe cold temperatures, but has a relatively low tolerance to warm temperatures. Previous studies have documented changes in habitat use by moose due to high temperatures. In many of these studies, the used areas have been classified according to how much thermal cover they were assumed to offer based on satellite/aerial imagery data. Here, we identified the vegetation structure in the areas used by moose under different thermal conditions. For this purpose, we used airborne laser scanning (ALS) data extracted from the locations of GPS‐collared moose. This provided us with detailed information about the relationships between moose and the structure of forests it uses in different thermal conditions and we were therefore able to determine and differentiate between the canopy structures at locations occupied by moose during different thermal conditions. We also discovered a threshold beyond which moose behaviour began to change significantly: as day temperatures began to reach 20 °C and higher, the search for areas with higher and denser canopies during daytime became evident. The difference was clear when compared to habitat use at lower temperatures, and was so strong that it provides supporting evidence to previous studies, suggesting that moose are able to modify their behaviour to cope with high temperatures, but also that the species is likely to be affected by warming climate.